What is the treatment for a paracetamol (acetaminophen) overdose?

Treatment of Paracetamol (Acetaminophen) Overdose

N-acetylcysteine (NAC) is the definitive antidote for paracetamol overdose and should be administered as soon as possible, ideally within 8 hours of ingestion, to prevent or minimize hepatotoxicity. 1

Initial Assessment and Risk Stratification

1. Determine timing and amount of ingestion:

   • Obtain history of ingestion time and quantity
   • Note that patient histories are often unreliable regarding amount ingested 2
   • Consider all cases as potentially toxic if history is unclear 3

2. Laboratory assessment:

   • Measure serum paracetamol concentration (not before 4 hours post-ingestion) 1, 3
   • Obtain baseline liver function tests (AST, ALT, bilirubin)
   • Check prothrombin time/INR, creatinine, BUN, blood glucose, and electrolytes 3

3. Risk stratification using Rumack-Matthew nomogram:

   • Plot serum paracetamol level against time since ingestion (4-24 hours)
   • Treatment line: Values above 200 mcg/mL at 4 hours to 50 mcg/mL at 12 hours indicate potential toxicity 3
   • Use lower treatment threshold (25% below standard line) for high-risk patients 1, 4

Treatment Protocol

For acute single ingestion with known time:

1. If presentation is within 4 hours of ingestion:

   • Start NAC immediately if estimated dose exceeds 150 mg/kg or 12g (whichever is less) 2
   • Obtain serum paracetamol level at 4 hours post-ingestion
   • Continue or discontinue NAC based on nomogram results

2. If presentation is 4-24 hours post-ingestion:

   • Obtain immediate serum paracetamol level
   • Start NAC without waiting for results if history suggests significant ingestion 1, 3
   • Continue NAC if level is above treatment line on nomogram
   • Discontinue NAC if level is below treatment line and liver enzymes are normal

3. If presentation is >24 hours post-ingestion:

   • Start NAC immediately
   • Check liver function tests and paracetamol level
   • Continue NAC if there is any evidence of hepatotoxicity 1

NAC Administration:

Oral Protocol 3:

• Loading dose: 140 mg/kg
• Maintenance dose: 70 mg/kg every 4 hours for 17 additional doses
• Dilute 20% solution with diet soft drinks to 5% concentration
• If patient vomits within 1 hour of administration, repeat that dose
• For persistent vomiting, consider duodenal intubation or IV NAC

IV Protocol (commonly used outside US):

• More commonly used in UK and Canada 4
• Consider for patients with persistent vomiting or inability to tolerate oral medication

Special Situations

Repeated Supratherapeutic Ingestion (RSTI):

• Defined as multiple ingestions over >8 hours exceeding 4g/24 hours 1
• Treatment indications:
  • Serum paracetamol ≥10 mg/mL OR
  • Elevated liver enzymes (AST/ALT >50 IU/L) 1
• Higher mortality risk compared to acute single overdose 1

Extended-Release Formulations:

• May have delayed and prolonged absorption 1
• Consider obtaining a second paracetamol level 4-6 hours after the first
• Lower threshold for initiating and continuing NAC treatment

Unknown Time of Ingestion:

• Measure both paracetamol level and liver enzymes
• Initiate NAC if paracetamol is detectable or liver enzymes are elevated 1

Monitoring and Supportive Care

1. Laboratory monitoring:

   • Repeat liver function tests, prothrombin time, creatinine, BUN, glucose, and electrolytes daily 3
   • Continue monitoring until clinical improvement and declining transaminases

2. Supportive care:

   • Maintain fluid and electrolyte balance
   • Treat hypoglycemia if present
   • Administer vitamin K if prothrombin time ratio exceeds 1.5
   • Provide fresh frozen plasma if prothrombin time ratio exceeds 3.0 3
   • Avoid diuretics and forced diuresis 3

Critical Timing and Outcomes

• Mortality risk: Significantly higher when NAC treatment is delayed beyond 10-15 hours post-ingestion 1, 5
• Hepatotoxicity rates with NAC treatment:
  • 2.9% when treatment delay <8 hours
  • 6.1% when treatment delay <10 hours
  • 26.4% when treatment delay >10 hours 1

Common Pitfalls to Avoid

1. Relying solely on patient history - Always obtain paracetamol levels even in cases with uncertain history 6

2. Delayed treatment - Do not wait for laboratory results if significant ingestion is suspected; NAC is most effective when started within 8 hours 1, 5

3. Premature discontinuation of NAC - Continue treatment in patients with elevated liver enzymes even if paracetamol levels are undetectable 2

4. Missing non-standard formulations - Be aware of different international names (acetaminophen/paracetamol) and extended-release preparations 6

5. Underestimating repeated supratherapeutic ingestions - These can cause severe hepatotoxicity despite lower individual doses 1